Welcome
Support Centre
17 April 2014 
ISRCTN Register - International Standard Randomized Controlled Trial Number
Trial registration
Unique identification scheme
International databases
home  |   my details  |   ISRCTN Register  |   mRCT  |   links  |   information  |   news
Find trials
ISRCTN Register
tips on searching

Registration
New application
Updating record

Information
introduction
governing board
ISRCTN FAQs
data set
letter of agreement
request information
guidance notes
statistics

[ Print-friendly version ]
Standard vs Modified Drug Therapy in Renal Cancer
ISRCTN ISRCTN06473203
DOI 10.1186/ISRCTN06473203
ClinicalTrials.gov identifier
EudraCT number
Public title Standard vs Modified Drug Therapy in Renal Cancer
Scientific title A randomised multi stage, phase II/III trial of Standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the treatment of locally advanced and/or metastatic renal cancer
Acronym STAR
Serial number at source MO10/9353
Study hypothesis Current study hypothesis as of 15/05/2013:
The aim of the STAR trial is to evaluate the use of a modified sunitinib or pazopanib schedule compared to the standard sunitinib or pazopanib schedule, in patients with locally advanced and/or metastatic renal cancer.
The trial aims to determine whether a modified sunitinib or pazopanib schedule involving a drug-free interval is non-inferior in terms of 2 year overall survival (OS) and quality adjusted life year (QALY) (averaged over trial recruitment and follow-up) compared to sunitinib or pazopanib given according to the standard strategy.

Previous study hypothesis until 15/05/2013:
The aim of the STAR trial is to evaluate the use of a modified sunitinib schedule compared to the standard sunitinib schedule, in patients with locally advanced and/or metastatic renal cancer.
The trial aims to determine whether a modified sunitinib schedule involving a drug-free interval is non-inferior in terms of 2 year overall survival (OS) and quality adjusted life year (QALY) (averaged over trial recruitment and follow-up) compared to a sunitinib given according to the standard strategy.

Please note that as of 15/05/2013, the following changes were made to the trial record:
1. The public title was previously "Standard vs Modified Sunitinib Treatment in Renal Cancer"
2. The scientific title was previously "A randomised multi stage, phase II/III trial of sunitinib. Comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced and/or metastatic renal cancer"
Lay summary http://cancerhelp.cancerresearchuk.org/trials/trials-search/a-trial-comparing-2-ways-taking-sunitinib-for-advanced-kidney-cancer-star
Ethics approval NRES Committee North West Liverpool Central, 6th June 2011, REC application reference: 11/NW/0246
Study design Randomised controlled open label multicentre 3 stage trial
Countries of recruitment United Kingdom
Disease/condition/study domain Locally advanced and/or metastatic clear cell renal cancer
Participants - inclusion criteria Current inclusion criteria as of 15/05/2013:
1. Male or female aged ≥ 18 years old
2. Histological confirmation of predominantly clear cell renal cell cancer
3. Inoperable loco-regional or metastatic disease
4. No prior systemic therapy for advanced disease (inoperable loco-regional and/or metastatic disease)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. Uni-dimensionally measurable disease (RECIST criteria, see Appendix 3)
7. Full blood count:
7.1 Haemoglobin (Hb) ≥ 9 g/dl
7.2. Absolute Neutrophil Count (ANC) ≥ 1 x 109/l
7.3. Platelets ≥ 80 x 109/l
8. Renal biochemistry: measured or calculated GFR ≥ 30 ml/min
9. Hepatobiliary function
9.1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x ULN
9.2. Bilirubin (BR) ≤ 1.5 x ULN, or or in patients with Gilbertís syndrome BR ≤ x3 x ULN and, direct BR ≤ 35%
10. Provided written informed consent prior to any trial-specific procedures
11. Able and willing to comply with the terms of the protocol including:
11.1. Commencement of sunitinib or pazopanib within 3 days of randomisation
11.2. Temporarily stopping sunitinib or pazopanibif randomised to the DFIS arm
11.3. Capable of oral self-medication
11.4. Capable of reporting toxicity and completing quality of life (QoL) and medical resource utilisation (MRU) questionnaires
12. If female and of child-bearing potential, must:
12.1. Have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding
12.2. Agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib or pazopanib
13. If male with a partner of child bearing potential, must agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib or pazopanib
14. Allowed situations include:
14.1. Primary renal cancer in-situ or previous nephrectomy
14.2. Previous brain metastases treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT) or gamma knife with no subsequent evidence of progression (patients treated with whole brain radiotherapy are not eligible)
14.3. Previous treatment in the SORCE study providing on placebo arm and not active sorafenib arms
14.4. Previous radiotherapy and/or previous/ongoing bisphosphonates or bone anti-resorptive drugs for the treatment of symptomatic bony metastasis

Previous inclusion criteria until 15/05/2013:
1. Male or female aged ≥ 18 years old
2. Histological confirmation of predominantly clear cell renal cell cancer
3. Inoperable loco-regional or metastatic disease
4. No prior systemic therapy for advanced disease (inoperable loco-regional and/or metastatic disease)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. Uni-dimensionally measurable disease (RECIST criteria, see Appendix 3)
7. Full blood count:
7.1 Haemoglobin (Hb) ≥ 9 g/dl
7.2. Absolute Neutrophil Count (ANC) ≥ 1 x 109/l
7.3. Platelets ≥ 80 x 109/l
8. Renal biochemistry: measured or calculated GFR ≥ 30 ml/min
9. Hepatobiliary function
9.1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x ULN
9.2. Bilirubin (BR) ≤ 1.5 x ULN, or or in patients with Gilbertís syndrome BR ≤ x3 x ULN and, direct BR ≤ 35%
10. Provided written informed consent prior to any trial-specific procedures
11. Able and willing to comply with the terms of the protocol including:
11.1. Commencement of sunitinib within 3 days of randomisation
11.2. Temporarily stopping sunitinib if randomised to the DFIS arm
11.3. Capable of oral self-medication
11.4. Capable of reporting toxicity and completing quality of life (QoL) and medical resource utilisation (MRU) questionnaires
12. If female and of child-bearing potential, must:
12.1. Have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding
12.2. Agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib
13. If male with a partner of child bearing potential, must agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib
14. Allowed situations include:
14.1. Primary renal cancer in-situ or previous nephrectomy
14.2. Previous brain metastases treated with complete surgical resection or gamma knife with no subsequent evidence of progression (patients treated with whole brain radiotherapy are not eligible)
14.3. Previous treatment in the SORCE study providing on placebo arm and not active sorafenib arms
14.4. Previous radiotherapy and/or previous/ongoing bisphosphonates or bone anti-resorptive drugs for the treatment of symptomatic bony metastasis
Participants - exclusion criteria Current exclusion criteria as of 15/05/2013:
1. Pulmonary or mediastinal disease causing obstruction or bleeding/haemoptysis
2. Patients with an estimated life expectancy of <6 months
3. Known contraindications to sunitinib or pazopanib
4. No previous treatment with sunitinib, pazopanib or other tyrosine kinase inhibitor (including in the adjuvant setting)
5. Untreated brain metastases
6. Any concurrent or previous other invasive cancer that could confuse diagnosis (non-melanomatous skin cancer or superficial bladder cancer acceptable, for all other cases please discuss with Clinical Trials Research Unit (CTRU))
7. Hypersensitivity to sunitinib or pazopanib
8. Any concomitant medication or substances forming part of local ongoing care known to significantly affect, or have the potential to significantly affect, the activity or pharmacokinetics of sunitinib or pazopanib (see section 10.2 for further information on concomitant medications)
9. Poorly controlled hypertension despite maximal medical therapy
10. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the STAR trial, including gastro-intestinal abnormalities limiting effectiveness of orally administrated drugs, uncontrolled infections, current or recent history of clinically significant cardiovascular disease, significant haemorrhage or gastrointestinal perforation or fistula which, in the opinion of the local investigator, would render the patient unsuitable for standard sunitinib or pazopanib therapy

Previous exclusion criteria until 15/05/2013:
1. Pulmonary or mediastinal disease causing obstruction or bleeding/haemoptysis
2. Patients with an estimated life expectancy of <6 months
3. Known contraindications to sunitinib
4. No previous treatment with sunitinib or other tyrosine kinase inhibitor (including in the adjuvant setting)
5. Untreated brain metastases
6. Any concurrent or previous other invasive cancer that could confuse diagnosis (non-melanomatous skin cancer or superficial bladder cancer acceptable, for all other cases please discuss with Clinical Trials Research Unit (CTRU))
7. Hypersensitivity to sunitinib
8. Any concomitant medication or substances forming part of local ongoing care known to significantly affect, or have the potential to significantly affect, the activity or pharmacokinetics of sunitinib (see section 10.2 for further information on concomitant medications)
9. Poorly controlled hypertension despite maximal medical therapy
10. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the STAR trial, including gastro-intestinal abnormalities limiting effectiveness of orally administrated drugs, uncontrolled infections, current or recent history of clinically significant cardiovascular disease which, in the opinion of the local investigator, would render the patient unsuitable for standard sunitinib therapy
Anticipated start date 03/10/2011
Anticipated end date 03/04/2018
Status of trial Ongoing
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 210 patients for phase II feasibility, continuing to 1000 patients in phase III trial
Interventions Current interventions as of 15/05/2013:
Sunitinib: one cycle of treatment refers to 50mg (starting dose) od, days 1-28, repeated every 42 days.
Pazopanib: one cycle of treatment refers to 800mg (starting dose) od, days 1-42, repeated every 42 days.

All patients receive sunitinib or pazopanib and will be randomised to receive either drug according to either a Conventional continuation strategy (CCS) or drug-free interval strategy (DFIS)

Control arm: Conventional continuation strategy (CCS)
Patients continue sunitinib or pazopanib with regular radiological assessments every 12 weeks until protocol-defined progressive disease (PD) (RECIST), unacceptable cumulative toxicity or patient decision to stop treatment or withdraw from the study.

Research arm: Disease-free interval strategy (DFIS)
Patients stop treatment and continue 6 weekly active surveillance (clinical assessment) and 12 weekly radiological assessment, with planned recommencement of sunitinib or pazopanib at the time of progressive disease (PD) (RECIST). Assuming further disease control, sunitinib or pazopanib is then continued again until the time of maximal radiological response and for a minimum of 4 cycles. At this point, assuming ongoing disease control, sunitinib or pazopanib can be again temporarily stopped until evidence of PD (RECIST) when again sunitinib or pazopanib is restarted. This DFIS is continued until PD occurs during sunitinib or paozpanib treatment, cumulative toxicity or patient decision to stop treatment or withdraw from the study.

Previous interventions until 15/05/2013:
Sunitinib: one cycle of treatment refers to 50mg (starting dose) od, days 1-28, repeated every 42 days.

All patients receive sunitinib and will be randomised to receive it according to either a Conventional continuation strategy (CCS) or drug-free interval strategy (DFIS)

Control arm: Conventional continuation strategy (CCS)
Patients continue sunitinib with regular radiological assessments every 12 weeks until protocol-defined progressive disease (PD) (RECIST), unacceptable cumulative toxicity or patient decision to stop treatment or withdraw from the study.

Research arm: Disease-free interval strategy (DFIS)
Patients stop treatment and continue 6 weekly active surveillance (clinical assessment) and 12 weekly radiological assessment, with planned recommencement of sunitinib at the time of progressive disease (PD) (RECIST). Assuming further disease control, sunitinib is then continued again until the time of maximal radiological response and for a minimum of 4 cycles. At this point, assuming ongoing disease control, sunitinib can be again temporarily stopped until evidence of PD (RECIST) when again sunitinib is restarted. This DFIS is continued until PD occurs during sunitinib treatment, cumulative toxicity or patient decision to stop treatment or withdraw from the study.
Primary outcome measure(s) 1. Stage A: Recruitment rate/month
2. Stage B: Time to Strategy Failure (TSF)
3. Stage C/Overall: 2 year OS and averaged QALY (over recruitment and follow up)
Secondary outcome measure(s) 1. Time to strategy failure (TSF)
2. Summative progression free interval (SPFI)
3. Cost effectiveness (health economic endpoints)
4. Toxicity
5. Quality of Life (FACT-G, FSKI-15, EQ-5D and EQ-VAS)
6. Progression free survival (PFS)

Ancilliary study: Translational: tissue and imaging
Sources of funding National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (Grant Ref: 09/91/21)
Trial website
Publications 1. 2012 protocol in http://www.ncbi.nlm.nih.gov/pubmed/23241439
Contact name Dr  Janet  Brown
  Address Cancer Research UK Clinical Centre
St James's University Hospital
Beckett Street
  City/town Leeds
  Zip/Postcode LS9 7TF
  Country United Kingdom
Sponsor University of Leeds (UK)
  Address University of Leeds
  City/town Leeds
  Zip/Postcode LS2 9JT
  Country United Kingdom
Date applied 15/04/2011
Last edited 15/05/2013
Date ISRCTN assigned 15/04/2011
Submit your trial protocol
Submit to Trials journal
Follow us on Twitter
© 2014 ISRCTN unless otherwise stated.